81831-47-2Relevant academic research and scientific papers
Antiarthritic and suppressor cell inducing activity of azaspiranes: Structure-function relationships of a novel class of immunomodulatory agents
Badger,Schwartz,Picker,Dorman,Bradley,Cheeseman,DiMartino,Hanna,Mirabelli
, p. 2963 - 2970 (2007/10/02)
Spirogermanium (1;8,8-diethyl-N,N-dimethyl-2-aza-8-germaspiro[4.5]decane-2-propanamin e dihydrochloride) is a potent cytotoxic agent in vitro which has demonstrated limited activity in experimental animal tumor models. Subsequently, it has been reported that spirogermanium has antiarthritic and suppressor cell-inducing activity. We have synthesized a series of substituted 8-hetero-2-azaspiro[4.5]decane and 9-hetero-3-azaspiro[5.5]undecane analogues of spirogermanium to identify the heteroatom requirements for in vivo antiarthritic and suppressor cell-inducing activity. This structure-activity relationship study has identified that appropriately substituted silicon and carbon analogues of spirogermanium retain both antiarthritic and immunosuppressive activity, with the 8,8-dipropyl (carbon) analogue being among the most active. Following the identification of N,N-dimethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2-propanamine dihydrochloride (9) as more active analogue than spirogermanium, a series of 8,8-dipropyl analogues with various amine substituents were synthesized. A number of these analogues had activity similar to that of 9. A correlation between activity in the adjuvant arthritic rat and the ability to induce suppressor cells (r = 0.894, p0.001) suggests an association between the two pharmacologic effects. While the precise biochemical mechanism(s) for the pharmacological activity is unclear, these data suggest that compounds within this series, e.g., N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine dihydrochloride, may provide effective therapy in diseases of autoimmune origin and/or the prevention of rejection in tissue transplantation.
Stereochemistry of 1,4-Addition of Nucleophiles to Ethyl Cyclohexylidenecyanoacetates
Nasipuri, Dhanonjoy,Sarkar, Ashis,Konar, Samir K.
, p. 2840 - 2845 (2007/10/02)
The stereochemistry of 1,4-addition of several nucleophiles such as cyanide, sodium borohydride, and methylmagnesium iodide to three substituted ethyl cyclohexylidenecyanoacetates (1-3) has been determined.A higher preference for equatorial attack is observed in these compounds than in related cyclohexanones, which is considerably diminished by the use of aprotic polar solvents.The results do not show any appreciable contribution of product stability control, recently shown to be important for hydride reduction of cyclohexanones, and have been rationalized on thebasis of a six-center cyclic transition state in which steric factors play a dominant role.These compounds have also been reduced by catalytic hydrogenation (Pd/C), and, interestingly, with unhindered systems (1, 2) hydrogenation takes place more from the axial side (40-60percent) as compared to cyclohexanones.
